Cancers of the oral cavity and pharynx are a major cause of death from cancer in the U.S., exceeding the U.S. death rates for cervical cancer, malignant melanoma and Hodgkin's disease. According to the American Cancer Society's Department of Epidemiology and Surveillance, an estimated 30,750 new cases of oral cancer were diagnosed in the U.S. during 1997, a figure which accounts for 2% to 4% of all cancers diagnosed annually.
Cancers of the esophagus are also difficult to determine and are frequently not observable until an advanced state of the disease, often being too late for the patient to be effectively treated. In such regions of the body, it is the metaplastic glandular epithelium which needs to be examined at an early stage. Preferably, and in accordance with the teachings of this intention, such examination and cellular detection is achieved without lacerational techniques and employs a brush biopsy to pick up the desired cellular sample.
Despite advances in surgery, radiation, and chemotherapy, the mortality rate of oral cancer has not improved in the last 20 years. Ultimately, 50% of patients die from their malignancy, and 8,440 U.S. deaths were predicted for 1997. There are several reasons for the high mortality rate from oral cancer, but undoubtedly, the most significant factor is delayed diagnosis. Studies have demonstrated that the survival and cure rate increase dramatically when oral cancer is detected at an early stage. For example, the 5-year survival rate for patients with localized disease approximates 79% compared to 19% for those with distant metastases. Unfortunately, approximately two thirds of patients at time of diagnosis have advanced disease, and over 50% display evidence of spread to regional lymph nodes and distant metastases.
Delay in the diagnosis of oral and pharynx cancer is often the result of the limited diagnostic tools available in the prior art. The dentist or physician who detects such a lesion which is not clearly suggestive of a precancer or cancer clinically, and who is limited to the prior art tools and methods, is faced with a quandary. Approximately 5–10% of adult patients seen in a typical dental practice exhibit some type of oral lesion, yet only a small proportion (approximately 0.5% to 1%) are precancerous or cancerous. These oral lesions are commonly evidenced as a white or reddish patch, ulceration, plaque or nodule in the oral cavity. The overwhelming majority of these lesions are relatively harmless; however, the multitude of poorly defined lesions in the oral cavity can be confounding to the clinician. A diverse group of oral lesions may be easily confused with malignancy, and conversely, malignancy may be mistaken for a benign lesion. Benign tumors, reactive processes, traumatic lesions, oral manifestations or systemic diseases, inflammatory oral disorders, and bacterial, viral and fungal infections all display similar oral features thereby impeding establishment of an accurate clinical diagnosis.
The only reliable means currently available in the prior art to determine if a suspect oral lesion is pre-cancerous or cancerous, is to incise or excise (i.e. lacerate) the lesion surgically with either a scalpel or a laser so that a histological section of the removed tissue can be prepared for microscopic evaluation. Histology can be generally defined as the microscopic inspection or other testing of a cross section of tissue. This prior art form of oral surgical biopsy is generally performed by a surgeon, and is often inconvenient, painful, and expensive.
In many environments, endoscopes are used to examine interior parts of the body which are inaccessible to ordinary visual observation. Observation of these inner parts with an endoscope is for purposes of locating pathological areas, trying to identify them using the endoscopic visual instrument and determining how to diagnose and treat such visualized areas. Cancer in various portions of the body may be apparent to a visual observer because of certain lesions appearing at the visualized tissue in the organ or area being observed.
Since the majority of oral abnormalities detected clinically prove benign when tested microscopically, and given the limitations of biopsy, including cost, inconvenience, pain and potential for complications, relatively few oral lesions are subjected to biopsy. It is primarily for this reason that only oral lesions with clinical features strongly suggestive of cancer or precancer are referred for biopsy as described in the prior art. As a result, many patients with ominous, but visually less suggestive lesions are allowed to progress to advanced oral cancer, with their condition undiagnosed and untreated.
The oral epithelium is substantially identical to the epithelium of the nasopharynx, hypopharynx, pharynx, trachea, larynx, and the upper esophagus. As a result, otolaryngology currently suffers from the effects of the same diagnostic dilemma which affects dentistry, i.e. the inability to clinically distinguish between common benign-appearing lesions and identically appearing pre-cancerous and early cancerous lesions. Thus, the only two cancers in the U.S. which have not improved in mortality in the last thirty years are oral cancer and laryngeal cancer.
Common, benign-appearing nose and throat lesions are usually noticed by the otolaryngologist during a routine, office examination of the throat which is typically conducted using a flexible nasopharyngoscope. This thin optical tube is easily threaded from the patent's nose into the throat and requires only a local anesthetic sprayed into the nose. This routine office procedure is performed by the average otolaryngologist many times each day.
The diagnostic dilemma for the otolaryngologist that is posed by the identical appearance of benign and pre-cancerous lesions is actually more acute than it is for the dentist. Although invasive and therefore avoided, a scalpel biopsy of the oral cavity is typically performed as an office procedure. Only local anesthetic is required, and bleeding from a scalpel biopsy of the oral cavity does not pose any aspiration danger. In contrast, a scalpel biopsy in many areas of the throat cannot be performed as an office procedure. This is because a scalpel biopsy in many areas of the throat may result in potentially dangerous aspiration of blood if the procedure is not performed under general anesthesia.
Referral of the patient for an operating room procedure requiring general anesthesia is both expensive and intrusive, and may expose the patient to other risks such as anesthesia and infection risk. The otolaryngologist is therefore hesitant to scalpel biopsy most benign-appearing throat lesions although they may represent the most treatable stage of a pre-cancer or cancer.
In many body sites, but not the oral cavity, a technique known as cytology is commonly utilized as an alternative to performing a lacerating biopsy and histological evaluation. In these body sites, pre-cancerous and cancerous cells or cell clusters tend to spontaneously exfoliate, or “slough off” from the surface of the epithelium. These cells or cell clusters are then collected and examined under the microscope for evidence of disease.
Since prior-art cytology is directed towards the microscopic examination of spontaneously exfoliated cells, obtaining the cellular sample is generally a simple, non-invasive, and painless procedure. Exfoliated or shed cells can often be obtained directly from the body fluid which is contiguous with the epithelium. Urine can thus be examined for evidence of bladder cancer, and sputum for lung cancer. Alternatively, exfoliated or shed cells may be obtained by gently scraping or brushing the surface of a mucus membrane epithelium to remove the surrounding mucus using a spatula or soft brush. This is the basis for the well known procedure known as the Pap smear used to detect early stage cervical cancer.
Because of the ease by which a cellular sample can be obtained from these body sites, prior-art cytology is typically utilized to screen asymptomatic populations for the presence of early stage disease. In the cervical Pap smear, for example, the entire surface area of the cervical regions where cancer generally occurs is gently scraped or brushed to collect and test the mucus from those regions. Abrasion of the underlying cervical epithelium is undesired, as it can cause bleeding and discomfort to the patient. This procedure is thus typically performed when no particular part of the cervix appears diseased, and when no suspect lesion is visible.
The design of prior art cytology sampling instruments reflects their use to sweep up cells which were spontaneously exfoliated and present on the superficial epithelial surface. Since prior-art cytology brushes need only to gently remove surface material, they are designed of various soft materials which can collect the cervical mucous with minimal abrasion to the underlying epithelium. These cytology sampling instruments therefore either have soft bristles, soft flexible fimbriated or fringed ends, or even, as in the case of the cotton swab or spatula, no bristles at all.
Examples of prior art cytological sampling tools include the wooden, metal or plastic spatula. According to the traditional method of Pap smear sampling, the spatula is placed onto the surface of the cervix and lightly depressed or scraped across the surface of the cervix to pick up exfoliated cells.
Further examples of prior art cytological sampling tools include the Cytobrush®; a device which uses soft and tapered bristles to sample shed cells from the cervical canal. U.S. Pat. No. 4,759,376, which allegedly covers this product, likewise describes a conical tapered soft bristle brush (a mascara brush shape) which is placed into the cervical canal and rotated for endocervical sampling. U.S. Pat. No. 4,759,376 teaches that the bristles “are to be relatively soft such as that of a soft toothbrush to more readily bend and avoid damaging the tissues.” By way of further example, physicians have long used the common swab, commercially known as the Q-Tip®, to perform endocervical sampling.
Other prior art cytological sampling tools designed to obtain a cytological sample from the cervix may combine both endocervical and exocervical sampling regions into one device. These devices swab the surface of mucous-covered tissue by soft brushing the mucous layer of the endocervix and exocervix at the same time, thereby collecting the cells contained in the mucous layer tissue of those surfaces. These devices include the Unimar®-Cervex Brush™, a brush that has a contoured flat comb-like head with a single layer of flexible plastic bristles (similar to a flat paint brush having only one row of bristles) in which the center bristles are longer than the bristles on the ends. According to the method of use for the device, the center bristles are inserted into the cervical canal until the lateral bristles bend against the exocervix. The device is then removed and the cells are swabbed across a microscope slide similar to painting with a paintbrush.
Similarly, the Bayne Pap Brush™, which Medical Dynamics, Inc. represents is covered by U.S. Pat. No. 4,762,133, contains a center arm, made of soft DuPont bristles, running horizontal to the cervical canal and a second arm of soft bristles at ninety degrees to the first arm, creating an L-shape. The center arm is placed within the cervical canal and then rotated. Upon rotation, the soft bristles of the second arm automatically sweep the surface of the exocervix in a circular motion thereby sampling the exocervix along with the endocervix.
Although cytology has been adopted for use in several other body sites, it has not been found useful to test questionable lesions of the oral areas. This is in large part due to the fact that the prior art devices and methods used to obtain a cellular sample for cytology are unsatisfactory when used to sample lesions of the oral and nasal areas and areas containing similar epithelia. Unlike the uterine cervix, questionable lesions of the oral cavity and similar epithelia may be typically coated with multiple layers of keratinized cells. This “keratin layer” forms a relatively hard “skin-like” coating over the surface of the lesion and may thus hide the abnormal cells lying underneath it and prevent their exfoliation from the surface.
As noted above, the design of prior art cytology sampling instruments reflect their use in tissues where spontaneously exfoliated abnormal cells are commonly present on the surface of an area of epithelium that harbors disease. These cytology sampling instruments therefore either have soft bristles, soft flexible fimbriated ends, or even no bristles at all. Since prior-art cytology brushes only need to gently remove surface material, they are designed of various soft materials which can collect the cervical mucous with minimal abrasion to the underlying epithelium.
While abnormal cells can spontaneously exfoliate to the epithelial surface and be gently removed by prior art instruments in the uterine cervix and other similar tissues, in many oral cavity lesions the abnormal cells never reach the surface because they are blocked by the keratin layer. This limitation is a major cause of the high false negative rate of prior art cytological testing to detect lesions of the oral cavity. That is, a large proportion of oral lesions found to be positive using lacerating biopsy and histology are found to be negative using cytology. In one major study, this false negative rate was found to be as high as 30%.
It is largely due to this lack of correlation between histology and prior art oral cytology that there is currently no significant use of oral cytology in the United States or elsewhere to test questionable oral lesions. Since it is well known that dangerous, truly cancerous oral lesions may commonly be reported as “negative” using prior art cytologic sampling techniques, prior art cytologic techniques offer little as a reliable diagnostic alternative to the lacerating biopsy and histology.
In addition to investigation of squamous epithelium above, diseases such as GERD and other lower gastrointestinal tract areas is required in which glandular epithelium exists. A further use of this brush biopsy invention is to reach the lower gastrointestinal tract and generate a sufficient cell sample for appropriate computer diagnosis as taught by the parent application of this continuation-in-part patent application.
A keratinized layer exists in the upper portion of the esophageal tract, and there is a rough boundary between the keratinized layer and the glandular epithelium in that tract. Glandular epithelium exists in areas deep within the body which is not subject to the external environmental, as is squamous epithelium which is the tissue found on the skin, the mouth, etc. which is in regular contact with the outside environment. The structure of glandular epithelium is, thus, different from the squamous epithelical three layer structure previously identified in connection with the parent application of which this is a continuation in part.